Developments in recombinant DNA technology have enabled cloning and expression of foreign genes in yeast. The utility of yeasts such as Saccharomyces cerevisiae as hosts for expressing mammalian and other foreign polypeptides offers advantages lacking in more commonly used prokaryotic hosts such as Escherichia coli. For example, yeasts are capable of glycosylation while prokaryotic hosts are not. The genetic system of S. cerevisiae is well-characterized, as are the principles for controlling gene expression. Additionally, S. cerevisiae is generally approved by the Food and Drug Administration.
The great practical and economic utilities of the yeast host system have been the impetus to attempt to maximize yeast expression by identifying various promoter regions to direct transcription, various sequences to terminate transcription, and other regulatory sequences. For example, yeast alcohol dehydrogenase has been identified as having a single strong promoter which is highly useful in enabling the attainment of substantial levels of expression for a variety of genes in yeast [Hitzeman, et al., Nature, 295: 717-722 (1981)]. U.S. Pat. No. 5,139,936 discloses a cloning vector containing a foreign gene and the yeast galactosidase (GAL1) regulatory region and promoter in position to increase expression of the foreign gene. U.S. Pat. No. 5,089,398 discloses the use of the promoter region from the glyceraldehyde-3-phosphate dehydrogenase to control expression of a foreign polypeptide in yeast. Thus, it is capable of providing which permits the attainment of substantial levels of expression for a variety of genes in yeast.